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Iron deficiency is associated with the development of cardiovascular diseases (CVDs), and the relative iron deficiency induced by erythropoiesis-stimulating agents may prevent the improvement of prognosis. Therefore, we investigated the association between iron deficiency and cardiovascular events during long-acting erythropoiesis-stimulating agent therapy using transferrin saturation (TSAT), which is less susceptible to inflammation than ferritin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study included 1040 patients with non-dialysis-dependent CKD, aged\u2009\u2265\u200920 years, with a glomerular filtration rate\u2009&lt;\u200960 mL\/min\/1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      and hemoglobin\u2009&lt;\u200911 g\/dL, who were treated with darbepoetin alfa for 96 weeks. The patients were recruited in the BRIGHTEN Trial,\u00a0a multicenter, prospective, observational study conducted to evaluate erythropoiesis-stimulating agent resistance to darbepoetin alfa in treating anemia in non-dialysis-dependent CKD in a clinical setting.\u00a0The association between transferrin saturation and the cumulative incidence of cardiovascular events\u00a0was evaluated\u00a0using the Kaplan\u2013Meier method. To calculate the hazard ratio (HR), 95% confidence intervals (CI) and the Cox proportional hazards model were used.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Survival curve analysis for cardiovascular events indicated that patients with transferrin saturation\u2009\u2265\u200930% had a significantly better prognosis, with an adjusted hazard ratio of 0.34 (95% confidence interval 0.22\u20130.52). Stratified analysis revealed that patients with transferrin saturation of 30\u201340% had a significantly lower risk of cardiovascular events than those with transferrin saturation of 20\u201330%, even after a multivariate-adjusted hazard ratio of 0.33 (95% confidence interval 0.21\u20130.54).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Patients with CKD and transferrin saturation of 30\u201340% had significantly fewer cardiovascular events than those with transferrin saturation of 20\u201330% among patients treated with long-acting erythropoiesis-stimulating agents. Therefore, it may be useful to maintain higher transferrin saturation from the viewpoint of erythropoiesis-stimulating agent responsiveness and the reduction of cardiovascular events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s40620-024-02000-y","type":"journal-article","created":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T06:02:16Z","timestamp":1719554536000},"page":"2327-2335","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Impact of transferrin saturation on cardiovascular events in non-dialysis-dependent chronic kidney disease patients treated with darbepoetin alfa"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6633-0924","authenticated-orcid":false,"given":"Kentaro","family":"Nakai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoya","family":"Nishino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuo","family":"Kagimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ichiei","family":"Narita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,6,28]]},"reference":[{"issue":"3","key":"2000_CR1","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1111\/j.1523-1755.2004.00863.x","volume":"66","author":"A Mohanram","year":"2004","unstructured":"Mohanram A, Zhang Z, Shahinfar S, Keane WF, Brenner BM, Toto RD (2004) Anemia and end-stage renal disease in patients with type 2 diabetes and nephropathy. 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The study protocol was approved by the ethics committee of the main institution (Nagoya University, no.2014\u20130027) and of each institution (Niigata University, no.2023\u20130014; Japanese Red Cross Fukuoka Hospital, no.23021). The study was registered with Clinical Trials.gov (NCT02136563) and UMIN-CTR (UMIN000013464).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Written informed consent was obtained from all participants.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}